Biological pacemaker created by fetal cardiomyocyte transplantation

Area of Science:

• Cardiology
• Regenerative Medicine
• Biomedical Engineering

Background:

• Electronic pacemakers are standard treatment for heart rhythm disorders.
• Complete atrioventricular block necessitates a reliable pacing solution.
• Investigating cell-based therapies as an alternative to electronic devices.

Purpose of the Study:

• To assess the feasibility of using human atrial cardiomyocyte grafts as a biological pacemaker.
• To evaluate the integration and function of grafted cells in a large animal model.
• To determine if the biological pacemaker can be modulated by autonomic agents.

Main Methods:

• Dissociated male human atrial cardiomyocytes, including sinus nodal cells, were grafted into the left ventricle of female pigs.
• Complete atrioventricular block was induced via catheter ablation.
• Electrophysiological mapping and polymerase chain reaction were used to assess cell survival, integration, and pacing origin.

Main Results:

• Cell-grafted pigs exhibited a significantly higher idioventricular beat rate (86 bpm) compared to controls (30 bpm) after AV block creation (P<0.001).
• Isoprenaline administration increased the idioventricular rate in grafted pigs (86 to 117 bpm, P<0.01).
• Grafted male cells survived, integrated with host myocardium, and demonstrated pacing function originating from the injection site.

Conclusions:

• Xenografted human atrial cardiomyocytes can survive and integrate into the host myocardium.
• These cells function as a biological pacemaker in a large animal model.
• The pacing function is responsive to autonomic nervous system modulation.